Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release

Izabela Komarowska; David Coe; Guosu Wang; Robert Haas; Claudio Mauro; Madhav Kishore; Dianne Cooper; Suchita Nadkarni; Hongmei Fu; Daniel A. Steinbruchel; Costantino Pitzalis; Graham Anderson; Pat Bucy; Giovanna Lombardi; Ross Breckenridge; Federica M. Marelli-Berg

doi:10.1016/j.immuni.2015.05.014

Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release

Izabela Komarowska, David Coe, Guosu Wang, Robert Haas, Claudio Mauro, Madhav Kishore, Dianne Cooper, Suchita Nadkarni, Hongmei Fu, Daniel A. Steinbruchel, Costantino Pitzalis, Graham Anderson, Pat Bucy, Giovanna Lombardi, Ross Breckenridge, Federica M. Marelli-Berg^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

82 Citations (Scopus)

Abstract

Effector-T-cell-mediated immunity depends on the efficient localization of antigen-primed lymphocytes to antigen-rich non-lymphoid tissue, which is facilitated by the expression of a unique set of "homing" receptors acquired by memory Tcells. We report that engagement of the hepatocyte growth factor (HGF) receptor c-Met by heart-produced HGF during priming in the lymph nodes instructs Tcell cardiotropism, which was associated with a specialized homing "signature" (c-Met+CCR4+CXCR3+). c-Met signals facilitated Tcell recruitment to the heart via the chemokine receptor CCR5 by inducing autocrine CCR5 ligand release. c-Met triggering was sufficient to support cardiotropic Tcell recirculation, while CCR4 and CXCR3 sustained recruitment during heart inflammation. Transient pharmacological blockade of c-Met during Tcell priming led to enhanced survival of heart, but not skin, allografts associated with impaired localization of alloreactive Tcells to heart grafts. These findings suggest c-Met as a target for development of organ-selective immunosuppressive therapies.

Original language	English
Pages (from-to)	1087-1099
Number of pages	13
Journal	Immunity
Volume	42
Issue number	6
Early online date	9 Jun 2015
DOIs	https://doi.org/10.1016/j.immuni.2015.05.014
Publication status	Published - 16 Jun 2015

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Komarowska, I., Coe, D., Wang, G., Haas, R., Mauro, C., Kishore, M., Cooper, D., Nadkarni, S., Fu, H., Steinbruchel, D. A., Pitzalis, C., Anderson, G., Bucy, P., Lombardi, G., Breckenridge, R., & Marelli-Berg, F. M. (2015). Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release. Immunity, 42(6), 1087-1099. https://doi.org/10.1016/j.immuni.2015.05.014

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abstract = "Effector-T-cell-mediated immunity depends on the efficient localization of antigen-primed lymphocytes to antigen-rich non-lymphoid tissue, which is facilitated by the expression of a unique set of {"}homing{"} receptors acquired by memory Tcells. We report that engagement of the hepatocyte growth factor (HGF) receptor c-Met by heart-produced HGF during priming in the lymph nodes instructs Tcell cardiotropism, which was associated with a specialized homing {"}signature{"} (c-Met+CCR4+CXCR3+). c-Met signals facilitated Tcell recruitment to the heart via the chemokine receptor CCR5 by inducing autocrine CCR5 ligand release. c-Met triggering was sufficient to support cardiotropic Tcell recirculation, while CCR4 and CXCR3 sustained recruitment during heart inflammation. Transient pharmacological blockade of c-Met during Tcell priming led to enhanced survival of heart, but not skin, allografts associated with impaired localization of alloreactive Tcells to heart grafts. These findings suggest c-Met as a target for development of organ-selective immunosuppressive therapies.",

author = "Izabela Komarowska and David Coe and Guosu Wang and Robert Haas and Claudio Mauro and Madhav Kishore and Dianne Cooper and Suchita Nadkarni and Hongmei Fu and Steinbruchel, {Daniel A.} and Costantino Pitzalis and Graham Anderson and Pat Bucy and Giovanna Lombardi and Ross Breckenridge and Marelli-Berg, {Federica M.}",

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Komarowska, I, Coe, D, Wang, G, Haas, R, Mauro, C, Kishore, M, Cooper, D, Nadkarni, S, Fu, H, Steinbruchel, DA, Pitzalis, C, Anderson, G, Bucy, P, Lombardi, G, Breckenridge, R & Marelli-Berg, FM 2015, 'Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release', Immunity, vol. 42, no. 6, pp. 1087-1099. https://doi.org/10.1016/j.immuni.2015.05.014

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AU - Komarowska, Izabela

AU - Coe, David

AU - Wang, Guosu

AU - Haas, Robert

AU - Mauro, Claudio

AU - Kishore, Madhav

AU - Cooper, Dianne

AU - Nadkarni, Suchita

AU - Fu, Hongmei

AU - Steinbruchel, Daniel A.

AU - Pitzalis, Costantino

AU - Anderson, Graham

AU - Bucy, Pat

AU - Lombardi, Giovanna

AU - Breckenridge, Ross

AU - Marelli-Berg, Federica M.

PY - 2015/6/16

Y1 - 2015/6/16

N2 - Effector-T-cell-mediated immunity depends on the efficient localization of antigen-primed lymphocytes to antigen-rich non-lymphoid tissue, which is facilitated by the expression of a unique set of "homing" receptors acquired by memory Tcells. We report that engagement of the hepatocyte growth factor (HGF) receptor c-Met by heart-produced HGF during priming in the lymph nodes instructs Tcell cardiotropism, which was associated with a specialized homing "signature" (c-Met+CCR4+CXCR3+). c-Met signals facilitated Tcell recruitment to the heart via the chemokine receptor CCR5 by inducing autocrine CCR5 ligand release. c-Met triggering was sufficient to support cardiotropic Tcell recirculation, while CCR4 and CXCR3 sustained recruitment during heart inflammation. Transient pharmacological blockade of c-Met during Tcell priming led to enhanced survival of heart, but not skin, allografts associated with impaired localization of alloreactive Tcells to heart grafts. These findings suggest c-Met as a target for development of organ-selective immunosuppressive therapies.

AB - Effector-T-cell-mediated immunity depends on the efficient localization of antigen-primed lymphocytes to antigen-rich non-lymphoid tissue, which is facilitated by the expression of a unique set of "homing" receptors acquired by memory Tcells. We report that engagement of the hepatocyte growth factor (HGF) receptor c-Met by heart-produced HGF during priming in the lymph nodes instructs Tcell cardiotropism, which was associated with a specialized homing "signature" (c-Met+CCR4+CXCR3+). c-Met signals facilitated Tcell recruitment to the heart via the chemokine receptor CCR5 by inducing autocrine CCR5 ligand release. c-Met triggering was sufficient to support cardiotropic Tcell recirculation, while CCR4 and CXCR3 sustained recruitment during heart inflammation. Transient pharmacological blockade of c-Met during Tcell priming led to enhanced survival of heart, but not skin, allografts associated with impaired localization of alloreactive Tcells to heart grafts. These findings suggest c-Met as a target for development of organ-selective immunosuppressive therapies.

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JF - Immunity

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ER -

Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release

Abstract

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